“Feel Good” Chemical Serotonin Signals Future Rewards to Brain: Study

April 23, 2025

Serotonin neurons signal to the brain the expected value of near-future rewards, a discovery that helps to clarify the neurotransmitter’s complex role in regulating mood, learning, and more, according to a new study in Nature. ¹ The research puts forth a unifying theory that makes sense of previously irreconcilable contradictions regarding the understanding of how serotonin functions, based on what its interdisciplinary team of scientists from the University of Ottawa calls a “prospective code for value.”

Serotonin, involved in the regulation of everything from mood and movement to appetite and sleep, has been historically deemed a “feel good” chemical. However, previous research revealed that serotonin is activated by pleasure, pain, and surprise, a finding that led scientists to suspect that its role in the central nervous system is more complex than was previously understood.

The Canadian researchers combined ideas from reinforcement learning theory (used to understand learning, behavior, and decision making) with insights into the properties of the dorsal raphe nucleus (the region of the brain containing neurons that release serotonin) to arrive at a nuanced understanding of the messages sent by the serotonin system.

The study found that serotonin tells the brain what reward to expect in the near future, information the brain needs to make decisions about what to do next. This function of serotonin may resemble that of dopamine, which is centrally involved in reward prediction. In fact, the authors were inspired by advances in the dopamine research field, which have paved the way for research of this kind.²

“Your brain needs to compute the expected value of the actions you contemplate and undertake as you interact with a changing world,” explains Jean-Claude Béïque, Ph.D., co-author of the study and professor in the Department of Cellular and Molecular Medicine. “What we think serotonin actually does in the brain is encode the expected value of a particular environment or course of actions in order to ultimately guide everyday decisions.”

This unifying theory explains why serotonin neurons are activated by both rewards and punishments, why they are more strongly activated by surprising rewards but not by surprising punishments and why negative uncertainty results in slow changes in neuron activity.

According to the study’s lead author, Emerson Harkin, Ph.D., the serotonin system is essentially updating the brain with the following message: “Here’s our best guess about how good your near future will be, and here’s how quickly that guess is improving.”

“Serotonin might promote patient waiting by increasing perceived reward availability,” the authors write regarding the brain’s response to the serotonin-fueled information it receives. “Whether serotonin sustains reward-seeking behavior in general, and how this relates to behavioral reinforcement, remains unclear.”

Implications for Understanding ADHD, Depression, and More

This new research may impact scientific thinking about ADHD, which impacts the brain’s reward system.

“Key aspects of the dopamine reward system are underactive in ADHD brains, making it difficult to derive reward from ordinary activities,” explains Ellen Littman, Ph.D., in the ADDitude article “Never Enough? Why ADHD Brains Crave Stimulation.” “Deficits in the reward pathway, including decreased availability of dopamine receptors, decrease motivation. Indeed, ADHD brains struggle to sustain motivation when rewards are mild or are linked to long-term gratification.”

The research may also inform the treatment of mood disorders like depression, in which serotonin is thought to play a central role. Selective serotonin reuptake inhibitors (SSRIs) that increase levels of serotonin in the brain are the first-line treatment for depression, which affects 21.9 million adults in the U.S (8.5% of all adults).³

Among individuals with ADHD, depression is the second most common comorbidity. The risk of developing depression is about 2.5 times higher for people with ADHD than it is for the general population. What’s more, for people with mood disorders, having comorbid ADHD is associated with an earlier onset of depression, more recurrent episodes, more frequent hospitalizations, and higher risk of suicide.⁴

It’s unclear whether the new research will impact interventions for depression or neurodevelopmental disorders, however a deeper understanding of what Harkin calls the brain’s “notoriously difficult to understand” neurons is noteworthy.

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